The goal of the Animal Resources core will be to generate and maintain transgenic mouse lines derived from genetically manipulated embryonic stem (ES) cells lines that will be developed in Projects II and III. The core will also provide animals for analysis, testing, and mating as needed by Program II, III, IV and Core B. Primarily, mouse lines will be generated through blastocyst injection of ES cells, however, this core will also be able to generate standard transgenic mouse lines through pronuclear microinjection of DNA constructs, as necessary. It is estimated that two to three ES cell lines will be injected for each construct and that one to two lines of mice will be maintained for each construct, depending on the phenotype and expression levels in each line. The Core will maintain breeding stocks and study animals for six transgenic mouse lines and appropriate control strains that are currently under study in Program II and III and Core B. The Core will also provide animals for mating by Project IV. The Core will oversee DNA typing, breeding record, and pedigrees for these lies and all subsequent lines that are developed by the project. The Animals Core will also maintain breeding stocks of C57BL/6J mice for production of blastocysts and CD-1 females and vasectomized males for production of pseudopregnant host females. Breeding stocks of FVB/NJ mice and a transgenic line of FVB/NJ mice carrying a pSV40tkneo construct will be maintained to provide embryonic fibroblast feeder cells for maintenance and selection of ES cells. The average daily census for the Animal Core is expected to be 500. All animals will be maintained in micro-isolator cages in a pathogen-free facility at the Johns Hopkins Medical School. The Animal Core w ill also be able to maintain frozen stocks of embryos from transgenic lines that are no longer needed for immediate production of study animals.